Three major enzymes, monoamine oxidase, catechol-O-methyltransferase and phenolsulfortransferase, are responsible for inactivation of the catecholamine neurotransmitters. All but the latter enzyme have been extensively studied in human brain whereas phenolsulfotransferase although also shown to be present in human CNS has not been well characterized nor has its role in this catabolic process been defined. Based on the lack of information concerning this transferase in human brain, the major objective of the study proposed will be: 1) Characterization of human brain phenolsulfotransferase. 2) Determine the metabolic fate of the sulfate esters of dopamine and norepinephrine in human brain. 3) Determine the ability of the hydroxylated metabolites of tricyclic drug to inhibit human brain phenolsulfotransferase. The following methods will be used to characterize phenolsulfotransferase: 1) Purify human brain phenolsulfotransferase and determine substrate specificity. 2) Determine whether the sulfate esters of dopamine and norepinephrine are metabolized by human brain monoamine oxidase and/or catechol-O-methyltransferase. 3) Perform inhibitory studies of phenolsulfotransferase with a variety of hydroxylated phenothiazine and tricyclic antidepressant analogs.